We conducted a large randomized clinical trial (the "Mashi Study") among HIV-infected women and their infants in Botswana, to evaluate peripartum antiretroviral prophylaxis strategies and infant feeding approaches that would minimize mother to children transmission (MTCT) of HIV-1 while optimizing infant survival. Short-course zidovudine (ZDV) was provided to mothers during pregnancy and to all infants for one month;mothers and infants were also randomized to receive single-dose nevirapine (sd NVP) or placebo at delivery/birth, and infants were randomized to either 6 months of breastfeeding + 6 months ZDV prophylaxis, or to formula feed (FF) with one month of ZDV. Exposure to sd NVP leads to NVP-resistant virus in most mothers and infants, and there is ongoing concern about the implications of this resistance for subsequent adult and pediatric NVP-based combination antiretroviral treatment (HAART) response. We collected (with informed consent and IRB approvals) supplementary data in this valuable cohort of mothers and infants in order to address additional important scientific objectives. We now propose using these data and samples to address the following new objectives, and need one year of additional funding to do this work: 1) To assess the proportion of women with virologic response (plasma HIV-1 RNA <400 copies / mL) by up to 36 months (3 years) after initiating NNRTI-containing ART among women who previously received single-dose NVP versus placebo during labor. 2) To assess the proportion of children with virologic response (plasma HIV-1 RNA <400 copies / mL) by up to 36 months (3 years) after initiating NNRTI-containing ART among infants who were previously exposed to peripartum, single-dose NVP. 3) To determine the proportion of infants with pre-HAART drug-resistant virus (among infants with and without exposure to single dose NVP), and to ascertain whether detectable baseline NVP drug resistance predicts subsequent failure. 4) To study pediatric growth and developmental outcomes, by infant HIV-1 status and by randomized feeding strategy, using abbreviated pediatric neurodevelopmental assessments (modified DST-II and PEDSTest) at 24 and 48 months of age as well as longitudinal growth data. 5) To study factors associated with repeat pregnancy, and maternal decision-making around repeat pregnancy. PUBLIC HEALTH RELEVANCE: Two million children are born to HIV-infected women each year, 420,000 children are newly infected with HIV-1 annually, and nearly 90% of all HIV-infected children live in sub-Saharan Africa [1]. Botswana, a southern African nation, has one of the world's highest HIV-1 infection rates;in 2005, HIV seroprevalence among pregnant women was 33.4% [2]. Studies related to the impact of MTCT prevention interventions on maternal and infant health and subsequent treatment options are therefore critical. The purpose of this application is to answer several new, important clinical research questions using data and samples that were collected in a randomized clinical trial (the "Mashi Study") in Botswana. The proposed new objectives pertain to HIV-1 drug resistance among HIV-infected infants with prior single-dose nevirapine exposure around the time of birth;long-term (up to 6-year) antiretroviral treatment outcomes among HIV-infected women and infants with prior single-dose nevirapine vs. placebo exposure;and pediatric neurodevelopmental and growth outcomes, by infant feeding modality and antiretroviral exposure history.